NM_001005289.5:c.830T>C

Variant names:

• chr11-5544676-A-G
• rs7934354
• NM_001005289.5:c.830T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005289.5(OR52H1):​c.830T>C​(p.Met277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,613,792 control chromosomes in the GnomAD database, including 6,349 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (979 hom., cov: 32)
  • Exomes 𝑓: 0.040 (5370 hom.)
• Consequence: OR52H1 NM_001005289.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 17 publications found

Genes affected

OR52H1 (HGNC:15218): (olfactory receptor family 52 subfamily H member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ENSG00000239920 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040930808).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005289.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52H1	NM_001005289.5	MANE Select	c.830T>C	p.Met277Thr	missense	Exon 2 of 2	NP_001005289.2	Q8NGJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52H1	ENST00000322653.7	TSL:6 MANE Select	c.830T>C	p.Met277Thr	missense	Exon 2 of 2	ENSP00000326259.5	A0A126GWQ6
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*739+46149T>C		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3
	OR52H1	ENST00000641796.2		c.830T>C	p.Met277Thr	missense	Exon 1 of 1	ENSP00000493308.2	Q8NGJ2

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11752 AN: 151898 Hom.: 979 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0670

GnomAD2 exomes AF: 0.0809 AC: 20330 AN: 251442 AF XY: 0.0778

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.0361

Gnomad EAS exome AF: 0.360

Gnomad FIN exome AF: 0.0588

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0403 AC: 58886 AN: 1461776 Hom.: 5370 Cov.: 31 AF XY: 0.0419 AC XY: 30485 AN XY: 727206

African (AFR) AF: 0.155 AC: 5181 AN: 33392

American (AMR) AF: 0.100 AC: 4492 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0376 AC: 983 AN: 26136

East Asian (EAS) AF: 0.414 AC: 16433 AN: 39698

South Asian (SAS) AF: 0.118 AC: 10156 AN: 86248

European-Finnish (FIN) AF: 0.0549 AC: 2931 AN: 53420

Middle Eastern (MID) AF: 0.0583 AC: 336 AN: 5768

European-Non Finnish (NFE) AF: 0.0133 AC: 14783 AN: 1111996

Other (OTH) AF: 0.0595 AC: 3591 AN: 60394

GnomAD4 genome AF: 0.0774 AC: 11772 AN: 152016 Hom.: 979 Cov.: 32 AF XY: 0.0821 AC XY: 6099 AN XY: 74322

African (AFR) AF: 0.140 AC: 5806 AN: 41332

American (AMR) AF: 0.0869 AC: 1327 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2014 AN: 5178

South Asian (SAS) AF: 0.131 AC: 633 AN: 4830

European-Finnish (FIN) AF: 0.0539 AC: 571 AN: 10592

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0161 AC: 1096 AN: 68022

Other (OTH) AF: 0.0687 AC: 145 AN: 2110

Alfa AF: 0.0407 Hom.: 2158

Bravo AF: 0.0867

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.139 AC: 611

ESP6500EA AF: 0.0199 AC: 171

ExAC AF: 0.0817 AC: 9918

Asia WGS AF: 0.252 AC: 874 AN: 3478

EpiCase AF: 0.0192

EpiControl AF: 0.0190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Benign	0.21	T
REVEL	Benign	0.16
Polyphen		0.46	P
MPC		0.027
ClinPred		0.058	T
GERP RS		5.2
Varity_R		0.69
gMVP		0.27
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7934354; hg19: chr11-5565906; COSMIC: COSV59505476;